Efficacy, Safety and Tolerability of VS-01 in Adult Patients With Acute-on-Chronic Liver Failure and Ascites (UNVEIL-IT)™

A Phase 2a, Open-label, Randomized, Controlled, Multi-Center Study to Assess the Efficacy, Safety and Tolerability of VS-01 on Top of Standard of Care (SOC), Compared to SOC Alone, in Adult Patients With Acute-on-Chronic Liver Failure (ACLF) Grades 1 and 2 and Ascites

A Phase 2, multi-center, randomized, controlled, open-label study to evaluate the effects of the intraperitoneal, liposomal formulation VS-01 in patients with an acute episode of hepatic and/or extrahepatic organ dysfunctions and failures in the presence of liver cirrhosis (Acute-on-Chronic Liver Failure, ACLF) and accumulation of fluid in the abdominal cavity (ascites)

Study Overview

• Status: Recruiting
• Conditions: Acute-On-Chronic Liver Failure; Ascites
• Intervention / Treatment: Drug: VS-01 on top of SOC; Other: SOC (Control Group)

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Carol Addy, MD
• Study Contact Backup: Name: Versantis AG, Katharina Staufer, MD; Phone Number: +333 20 16 40 00; Email: clinical@versantis.com

Study Locations

• Belgium
  • Flemish Brabant
    • Leuven, Flemish Brabant, Belgium, 3000
      • Recruiting
      • Universitair Ziekenhuis Leuven
  • Oost-Vlaanderen
    • Gent, Oost-Vlaanderen, Belgium, 9000
      • Recruiting
      • Universitair Ziekenhuis Gent
• France
  • Franche-Comte
    • Besançon Cedex, Franche-Comte, France, 25030
      • Recruiting
      • Centre Hospitalier Regional et Universitaire de Besancon - Hopital Jean-Minjoz
• Germany
  • Berlin, Germany, 13353
    • Recruiting
    • Charite Universitatsmedizin Berlin
  • Hannover, Germany, 30625
    • Recruiting
    • Medizinische Hochschule Hannover
  • Nordrhein-Westfalen
    • Muenster, Nordrhein-Westfalen, Germany, 48149
      • Recruiting
      • Universitatsklinikum Munster
  • Thüringen
    • Jena, Thüringen, Germany, 07747
      • Recruiting
      • Universitätsklinikum Jena
• Spain
  • Barcelona, Spain, 08036
    • Recruiting
    • Hospital Clínic de Barcelona
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospitali University Of Vall d'Hebron-Vall d'Hebron Research Institute (VHIR)
  • Madrid, Spain, 28034
    • Recruiting
    • Hospital Universitario Ramón y Cajal
  • Madrid, Spain, 28007
    • Recruiting
    • Hospital General Universitario Gregorio Maranon
  • Valencia, Spain, 46026
    • Recruiting
    • Hospital Universitari I Politecnic La Fe
• United States
  • Virginia
    • Richmond, Virginia, United States, 23249
      • Recruiting
      • Richmond VA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Cirrhotic patients diagnosed by standard clinical criteria, imaging findings and/or histology with any underlying etiology;
2. Cirrhotic patients with ACLF Grade 1 or 2 according to European Association for the Study of the Liver (EASL)-CLIF criteria as described in the EASL-Clinical Practice Guideline on decompensated liver cirrhosis (EASL Clinical Practice Guidelines, 2018);
3. Onset of ACLF not more than 96 h before Screening (SCR);
4. Presence of ascites requiring paracentesis;
5. Patients with body mass index (BMI) < 35 kg/m²;
6. Written informed consent obtained prior to the start of any study-related procedures.

Exclusion Criteria:

1. Patients with acute or sub-acute liver failure without underlying cirrhosis;

2. Presence of the following organ(s) failure(s) as per the EASL definitions and/or adapted from CLIF-C Organ Failure (CLIF-C OF)/CLIF-Sequential Organ Failure Assessment (CLIF-SOFA) scores:

   1. Respiratory failure;
   2. Coagulation failure;
   3. Severe cardiovascular failure requiring the use of vasopressors;
3. ACLF grade 3: Presence of three or more organ failures as per EASL CLIF criteria as described in the EASL-Clinical Practice Guideline on decompensated liver cirrhosis;
4. Presence of spontaneous or secondary bacterial peritonitis;
5. Presence of spontaneous bacterial pleural empyema;
6. Patients with medical history of spontaneous bacterial peritonitis over the past 4 weeks;
7. Known active tuberculosis, or latent tuberculosis requiring treatment;
8. Presence of uncontrolled severe infection at SCR or Baseline (BL);
9. Patients with seizure disorder;
10. Patients with history of upper gastro-intestinal bleeding over the past 2 weeks, acute bleeding or bleeding upon paracentesis at SCR or BL;
11. Contraindication for paracentesis;
12. Coagulation disorders such as disseminated intravascular coagulation, hemophilia, known congenital or acquired Von Willebrand disease or platelet function defects;
13. Transjugular intrahepatic portosystemic shunt procedure or any major abdominal surgery having occurred in the past 4 weeks prior to SCR;
14. Potential or known hypersensitivity to liposomes;
15. Potential or known risk factors for allergic/anaphylactoid like reactions (e.g., mastocytosis/elevated basal tryptase) or multiple hypersensitivities;
16. Patients with known Porto-pulmonary hypertension and hepato-pulmonary syndrome;
17. Patients after organ transplantation receiving immunosuppressive medication;
18. Any severe disease considered to be potentially detrimental at the discretion of the Principal Investigator. This includes but is not limited to hepatocellular carcinoma outside Milan criteria, cholangiocarcinoma, extrahepatic cancer over the past 2 years, people who inject drugs or individuals formerly injecting drugs on substitution therapy;
19. Need for Renal Replacement Therapy or any extracorporeal liver support device (e.g., MARS®, Prometheus®, Plasmapheresis);
20. Alfapump® in place to manage ascites;
21. ACLF due to severe alcoholic steatohepatitis in patients with ongoing excessive alcohol intake with a Maddrey Score ≥ 32 requiring steroid treatment;
22. ACLF due to acute viral hepatitis A, B, B+D, C or E requiring antiviral treatment;
23. ACLF due to autoimmune hepatitis requiring high-dose steroid treatment;
24. Pregnancy and lactation;
25. Women of child-bearing potential who are not willing to use adequate contraception;
26. Patients who participate in another clinical trial at the time of SCR or within 4 weeks prior to SCR.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VS-01 on top of SOC (Active Treatment Group); Patients randomized to Active Treatment group will receive VS-01 on top of SOC	Drug: VS-01 on top of SOC; Patients will receive VS-01 intraperitoneally on four consecutive days on top of SOC
Other: SOC (Control Group); Patients randomized to Control group will receive SOC defined as the standard medical management of patients with decompensated cirrhosis and ACLF	Other: SOC (Control Group); Patients will receive SOC for decompensated cirrhosis and ACLF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Chronic Liver Failure Consortium (CLIF-C) ACLF score at Day 7	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to death through Days 28 and 90		Day 1 through Days 28 and 90
Change in ACLF grade through/at Days 7 and 28		Day 1 through Day 7 and Day 28, at Days 7 and 28
28-day and 90-day mortality		At Days 28 and 90
Transplant-free survival through/at Days 28 and 90		Day 1 through Days 28 and 90, at Day 28 and 90
Incidence rate, severity, and relationship to VS-01 of adverse drug reactions and serious adverse drug reactions.	Safety	Day 0 to Day 90

Collaborators and Investigators

• Sponsor: Versantis AG
• Investigators: Study Director: Katharina Staufer, MD, Versantis AG

Study record dates

Study Major Dates

• Study Start (Actual): July 2, 2023
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): November 1, 2024

Study Registration Dates

• First Submitted: June 2, 2023
• First Submitted That Met QC Criteria: June 2, 2023
• First Posted (Actual): June 12, 2023

Study Record Updates

• Last Update Posted (Actual): April 23, 2024
• Last Update Submitted That Met QC Criteria: April 22, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Cirrhosis; Renal Impairment; Hepatic Impairment; Chronic liver diseases; Liver Failure; Renal Disease; Hepatic Dysfunction; Extrahepatic Organ Dysfunction; Hepatic Decompensation
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Liver Failure, Acute; End Stage Liver Disease; Liver Failure; Hepatic Insufficiency; Acute-On-Chronic Liver Failure; Ascites
• Other Study ID Numbers: VS01-IIa-01; 2021-002617-33 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No